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.

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from the 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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

 Purpose

Through this non-competitive single source cooperative agreement notice of funding opportunity, the National Center for Advancing Translational Sciences (NCATS) solicits an application from the Cincinnati Childrens Hospital and Medical Center (CCHMC) for the continuation of the Rare Diseases Clinical Research Network (RDCRN) Data Management and Coordinating Center (DMCC). NCATS is supporting CCHMC for its ability to facilitate and support the advancement of rare disease research for each individual Rare Disease Clinical Research Consortia (RDCRC) and trans-network RDCRN efficiently and expeditiously. CCHMC has unique capabilities for managing the DMCC including:

• Integration with the Cloud Computing Services and Engineering Support provisioned by the NCATS Information Resources Technology Branch (ITRB).
• Established training programs for the more than 280 national and international institutions that participate in the RDCRN on establishing coordinated common data elements (CDE) and data standards that are based on the FAIR principles for data management that ensure that the data across the network RDCRC is findable, accessible, interoperable and reusable.
• An established cloud-based working environment for investigators, along with a public data sharing environment.
• Existing relationships and data transfer capabilities with existing RDCRC and the parent institute of the RDCRC.
• Existing databases for nearly 20 RDCRC with 57 ongoing studies to ensure the successful capture of data, using network data standards, in accordance with a broad array of protocols.
• Efficient communications and procedures for coordinating RDCRN activities.
• Experience facilitating and overseeing the coordinated sharing of study data with investigators from outside the study network.
• Existing policies that facilitate access to the data set while ensuring protection of potentially identifiable participant information.
• Established clinical research and administrative support.
• Experience in interacting with, and facilitating, interaction with diverse patient advocacy groups.

Rationale for Single Source

Extensive funds and resources have been expended by the NCATS DRDRI to create and optimize the current DMCC as a trusted, cohesive, efficient infrastructure for facilitating and supporting rare disease research. This includes integration with the Cloud Computing Services and Engineering support provisioned by the NCATS ITRB. NCATS ITRB has provided access to various public cloud services, and high-performance computing services for the needs of the DMCC. These resources have been developed and maintained by CCHMC enabling the DMCC to offer its systems, projects, and research in a secure environment with simplified implementation, deployment, and operational reliability to the RDCRN award recipients. It also includes development of the overall network itself, with its more than 280 diverse institutions (patient advocacy organizations, academia, hospitals, and more) that are trained by the DMCC on coordinated CDE and data standards. All data standards are based on the FAIR principles for data management to ensure the data across the network is findable, accessible, interoperable, and reusable. Any attempt to recreate the trusted and reliable DMCC anew would result in substantial delays in implementing new studies because of the time and effort required to re-establish the necessary infrastructure within the new entity and to make the connections with the DMCC resources that already exist for the RDCRN.

While NCATS recognizes and endorses the need for full and open competition, and by preference utilizes open competition in most of its initiatives, we believe that the investments made by the NIH and the proven effectiveness of the current DMCC in developing a broad bioinformatics infrastructure warrants an exception. To recapitulate the time and resources needed to recreate or transfer this infrastructure would be costly and would significantly reduce the pace with which innovative studies could be initiated and completed. Consequently, the serious disruptions in study planning and conduct that would result from such an endeavor would have adverse effects on bringing new potential treatments to patients expeditiously.

As such NCATS is announcing this notice of funding opportunity as a single source cooperative agreement, open only to CCHMC. The requested application will continue to cover the core elements of responsibility as identified in the prior open competition application solicitation (RFA-TR-18-021).  

Background

The Rare Diseases Act of 2002 (Public Law 107-280 (https://www.gpo.gov/fdsys/pkg/PLAW-107publ280/content-detail.html)) defines a rare disease as a condition affecting fewer than 200,000 individuals in the United States. Collectively there are estimated to be over 10,000 diseases or conditions that fall into this category; cumulatively, there are approximately 25 – 30 million people in the United States who are affected by rare diseases or conditions. Many of these disorders lead to significant morbidity and mortality. These facts highlight that rare diseases are a significant public health concern.

Despite advances in our understanding of the causes and mechanisms of many diseases, effective treatments are available for fewer than 5% of rare diseases. Although advances in technologies such as gene-based therapies have recently led to promising and potentially transformative treatments, these are currently limited to a few rare diseases.

Bringing effective treatments to more people living with rare diseases is a risk-filled venture for numerous reasons. First, making a diagnosis can be challenging with many patients experiencing a "diagnostic odyssey" of years because of limited knowledge of the range of disease manifestations and of genotype-phenotype correlations. Second, many rare diseases have a spectrum of phenotypes, and there are often no high-quality natural history datasets documenting how the disease affects patients' functioning and how it progresses over time. Third, the relatively small number of patients and clinicians caring for them leads to challenges in the design and implementation of clinical trials. Fourth, there are often no sensitive and specific outcome measures or biomarkers that are appropriate for use in clinical trials or that are clinically relevant to patient needs. Fifth, the data quality and the rigor of scientific studies are often lacking and usage of data standards and adherence to FAIR principles for data management vary across rare disease research making collaborations difficult. Finally, the resources available for therapeutics development are limited, making it critical to find frameworks for leveraging partnerships among patient groups, industry, academic investigators, and federal funding agencies. The global burden associated with rare diseases necessitates international coordination and collaboration.

To facilitate progress in addressing these challenges, the Rare Diseases Act of 2002 directed the DRDRI to support regional "RDCRCs of Excellence" for clinical research, career enhancement, and demonstration of diagnostic, prevention, control, and treatment methods for rare diseases. Since the inception of this legislation, numerous NIH ICOs (NCATS, NCRR, OD, NICHD, NINDS, NIAMS, NHLBI, NIDDK, NIDCR, NIMH, NCI, NIAID and NEI), led by the DRDRI at NCATS, have partnered to support the RDCRN. The RDCRN was established to be a collaborative and coordinated network of investigators and patient groups committed to the investigation of rare diseases working in partnership with leaders in technology to enhance communication and sharing of resources through a multidisciplinary approach.

To date, this program has successfully supported 33 individual RDCRCs that have conducted research on nearly 250 individual disorders. The research conducted within the RDCRN has contributed to the Food and Drug Administration (FDA) approval for eleven treatments for rare diseases.

Organization of the RDCRN

The RDCRN is a cooperative network composed of multiple Consortia (RDCRCs)  and a Data Management and Coordinating Center (DMCC) established to coordinate RDCRN activities and to support and facilitate clinical research in rare diseases conducted by the RDCRCs. The RDCRN functions as a collaborative network with each RDCRC establishing and maintaining an environment that fosters collaborative, patient-oriented, multi-site, multi-disciplinary research collaborations and career enhancement.

The activities of the RDCRN are coordinated, facilitated, and supported by the DMCC. Patient advocacy partners participate in individual RDCRC activities as well as participating in Coalition of Patient Advocacy Group (CPAG) activities. The RDCRN governance consists of three committees: the Network Steering Committee (SC), the CPAG SC and the Joint Leadership Team (JLT). These committees are described in detail in the "Governance" section. The committees consist of the PIs of each funded RDCRC, their affiliated patient advocacy group(s), the DMCC, and NIH program representatives including the NCATS RDCRN Program Director, Program Officials (PO) and Project Scientists (PS). All recipients of an RDCRC and their teams are members of the RDCRN, and as such are part of a national rare diseases research resource. Each RDCRC will be expected to actively participate in network activities, including meetings of the Steering committee, biennial RDCRC meetings, and various relevant workgroups (e.g., bioinformatics, engagement, dissemination of information).

Each RDCRC must be willing to work towards being a member of a network that supports common data standards, FAIR data practices across sites; encourage the use of CDE; commit to community engagement; and agree to share data and other resources to the network, the broader scientific research community, and the general public.

RDCRC Elements

Each RDCRC must focus on rare diseases. In this document, a rare disease is defined as one that affects fewer than 200,000 people in the United States (per the Rare Diseases Act 2003).

Each RDCRC application must indicate at least three different rare diseases that may share, but are not limited to, common pathways/mechanisms of action/organ system, and may be defined as:

• Conditions - a particular state of being that limits/restricts something else.
• Disorders - abnormal physical or mental conditions or ailments.
• Syndromes - a group of symptoms that occur together, or a condition characterized by a set of associated symptoms.
• Diseases - a disorder of structure or function that affects a specific location and is not simply a result of physical injury.

Each RDCRC is required to have one natural history or longitudinal study. Research studies must all be conducted at multiple sites; however, pilot studies may be conducted at a single site.

Applicants are encouraged to emphasize new ideas, novel approaches, and state-of-the-art technologies to address the needs for early diagnosis and effective treatments along with other strategies to improve the lives of individuals with rare diseases.

Applicants with research agendas at varying stages of scientific development within the research program are encouraged to apply. This includes groups that would be considered early-stage RDCRC with many knowledge gaps that need to be addressed (e.g., groups that do not yet have established registries, groups with poorly defined natural history data that would benefit from an RDCRC effort).

Each RDCRC must form partnerships with patient advocacy groups. These groups must participate as active members of the RDCRC with meaningful roles within the RDCRC and as members of the RDCRN CPAG.

RDCRC Structure
The structural requirements of an RDCRC under this NOFO are:

• Administrative Core
• Pilot/Feasibility Governance Core
• Career Enhancement Core
• 2-4 Clinical Research Projects

Coalition of Patient Advocacy Groups (CPAG)
The RDCRN CPAG was established to promote collaboration between rare disease patient and stakeholder organizations and the RDCRN to facilitate better access to, and earlier benefit from, research conducted on rare diseases. Each RDCRC must be actively engaged with the CPAG.

Any RDCRC patient advocacy group members may participate in RDCRN activities.  One patient advocacy group member from each RDCRC will be identified by the RDCRC to represent the consortia on the CPAG steering committee. As the patient advocacy arm of the RDCRN, CPAG members will use their position to advance the cause of rare disease research and improved patient outcomes through the network.

DMCC Structure
The platform for the DMCC resides within the NCATS Information Technology Resources Branch (ITRB) provided cloud resource. All software licenses belong to NCATS. This is an NCATS-furnished infrastructure that the award recipient will use as a platform on which to build the data management and coordination center. This protects the integrity of the data and allows the RDCRN DMCC system to stay in the same location regardless of future DMCC award recipients.

Overall, the goal of the DMCC is to provide support to each individual RDCRC, and to coordinate and support the activities of the RDCRN as a whole. The structural requirements of the DMCC are:

• Administrative Core to facilitate network operation, governance, and communication.
• Data Management Core to build and maintain a robust, secure data infrastructure.
• Clinical Research Core to provide guidance in developing best practices in clinical research, protocol development and good data practices using the FAIR principles.
• Engagement and Dissemination Core to promote patient engagement and broad research dissemination.

It is the responsibility of the investigative teams of the DMCC cores (Administrative Core, Data Management Core, Clinical Research Core, and Engagement and Dissemination Core) to work collaboratively with each RDCRC to coordinate and support both RDCRC activities and RDCRN-wide efforts (e.g., develop and monitor best practices for clinical and research data handling and use as well as data sharing).

The RDCRCs will collaborate with the DMCC to establish and promulgate coordinated RDCRN data management and data sharing standards and policies within the RDCRC.

It is imperative that the DMCC applicant carefully review the RDCRC NOFO (PAR-24-206) to fully understand the resources and services that will be provided to the network participants by the DMCC. Applicants should ensure planned activities involve coordination with the DMCC and do not replicate efforts.

Cores
Administrative Core

The investigative team of the Administrative Core is responsible for facilitating network operations, governance, and communication. Investigators are encouraged to convene a diverse, multidisciplinary, skilled team that provides synergy to the RDCRN by working together with both individual RDCRCs and across the RDCRN.

The investigative team of the Administrative Core will provide overall coordination for the RDCRCs and the management of RDCRN activities, including the Network SC, the JLT, the CPAG SC meetings, and bi-annual RDCRN network-wide meetings. It will also provide oversight and ensure the coordination of activities across all DMCC cores. The investigative team of the Administrative Core will be responsible for maintaining and disseminating the Network Operations Manual that defines roles, responsibilities, minimum network standards, and operational requirements for all RDCRN participants. They will also be responsible for preparing an all-inclusive RDCRN annual report to be made publicly available.

The investigative team of the Administrative Core, working collaboratively with the investigative team of the Data Management Core, will centrally track all research projects within the RDCRN including, but not limited to, pilot projects and the career enhancement program beneficiaries. This investigative team will also collaborate with the RDCRC to develop and promote the utilization of clinical trial readiness metrics for both regulatory requirements (e.g., protocols, Institutional Review Boards (IRBs)) and clinical research components (e.g., natural history studies outcome measures, biomarkers) to evaluate their progress in clinical trial readiness.

The investigative team of the Administrative Core will develop a plan and timeline for both onboarding RDCRC new to the network and transitioning groups that will complete their funding eligibility and transition off the RDCRN at the end of the funding cycle.

Data Management Core

Advancing rare disease research by freely sharing high-value data is a critical goal of the program.

Deidentified data collected within this network will become a resource for the greater rare disease research community and will be made available to the scientific community, stakeholders and other relevant partners in a timely manner that meets all NIH human subject's protection, data safety and data sharing requirement.

RDCRC participants are required to work collaboratively within the RDCRN DMCC cloud environment and to ultimately share their data within RDCRN Data Repository (RDCRN-DR).

The investigative team of the Data Management Core will support and enhance a collaborative informatics community for the RDCRN.

The DMCC will support the RDCRC by maintaining a robust secure data infrastructure for the RDCRN. The DMCC will work closely with NCATS to provide Cloud Computing Services and Engineering Support provisioned by the ITRB at NCATS. The DMCC will provide:

RDCRN Cloud-Based Working Environment

The investigative team of the Data Management Core, in collaboration with the investigative team of the Clinical Research Core, will provide:

• A management system for collection, storage, and quality control of clinical research data, including a web-based platform that allows for real-time tracking of data quality and completeness and that facilitates remote monitoring.
• A management system that provides a "virtual repository" that indexes existing biosamples and other resources within the network.
• A portal and tools establishing a "tool garden" of shared research tools for RDCRC investigators to access and manage their own data. Tools provided by NCATS are based on need and use and include, but are not limited to, Amazon Web Services, Atlassian, CODECOV, Facebook, Github, MAILCHIMP, Pantheon. Shippo, SHUTTERSTOCK, TWILIO, VIMEO PRO, Seven Bridges, Box.com.

Data Management Services

The investigative team of the Data Management Core will also manage and facilitate use of Cloud Computing Services and Engineering Support provisioned by the ITRB, NCATS.

NCATS ITRB will provide access to various public cloud services, and high-performance computing services for the needs of the RDCRN. The NCATS ITRB works directly with the DMCC. The DMCC is responsible for working with each individual RDCRC however, there may be special instances where the ITRB will work collaboratively with the DMCC and RDCRC (e.g., establishing use of a new tool in the cloud environment). This enables the DMCC to provide the RDCRCs systems, projects and research in a secure environment with simplified implementation, deployment and operational reliability. Through these services, NCATS ITRB will prepare the recipients to gain a self-service capability. 

The DMCC will access the cloud instance through the NCATS' Federated Authorization Services and will have complete rights to all services provided by the Cloud Service Provider.

The investigative team of the Data Management Core will coordinate and support efforts, in collaboration with representatives of the RDCRC, to develop and monitor Good Data Practices (GDP) of clinical and research data and will assist in facilitating the use of the FAIR principles for data management. The investigative team of the Data Management Core will collaborate with the investigative team of the Clinical Research Core to facilitate and coordinate data standards across the network.

NCATS will provide investigators who participated in the RDCRN, and shared data within the current RDCRN data environment, access to account management, tools, and data storage (provisioned by the DMCC) for their RDCRC data for up to five years post-award. Any custom development, setup, or data management will not be included; if needed, it can be provided by the former RDRCR, or a third party paid for by the former RDCRC. Access to this resource will be provided based upon application and NCATS approval.

Data Sharing Environment - The RDCRN-Data Repository (RDCRN-DR)

The RDCRN-DR will serve as the central repository for RDCRN-generated clinical research data. It will host consented research data from RDCRC-initiated natural history studies, interventional studies and trials, patient reported outcomes and other modalities that were obtained under RDCRN protocols. The RDCRN-DR will also function as a central indexing site for RDCRN data that may be required to reside in other NIH-based data repositories, such as the database of Genotypes and Phenotypes (dbGaP https://www.ncbi.nlm.nih.gov/gap/), National Database for Autism Research (NDAR https://nda.nih.gov/).

The DMCC will work with each RDCRC to ensure that data to be shared meets all quality control standards, uses RDCRN-wide data standards, provides all appropriate metadata and identifies all data use limitations. Individual RDCRCs will then be responsible for submitting the data into the NCATS Governed RDCRN-DR, along with a university signing official signature, within a time frame dictated by the applicable NIH data sharing policies, their funding IC, and NCATS. The investigative team of the RDCRC Administrative Core has the responsibility for certifying that submitted data is compliant with regulations and was obtained under the informed consent of the participants.

Once the data has been transferred to the RDCRN-DR NCATS becomes responsible for regulating access to the RDCRN-DR through a Data Access Committee (DAC) made up of Federal representatives. The DAC will meet regularly to adjudicate access requests and ensure that data is only made accessible if the requests are compatible with data use limitations for the data in question. NCATS hosts this cloud-based platform and ensures its long-term sustainability.

Because the DMCC supports and assists in data management of the RDCRN it is important that they work in collaboration and communicate regularly with NCATS. This is intended to ensure a smooth transition of data from the working environment to the shared RDCRN-DR environment. NCATS is responsible for the implementation, administration and maintenance and continued enhancement of the RDCRN-DR platform. The DMCC provides first-level support for the platform and executes standard, validated workflows on incoming data (e.g., for quality control (QC) purposes).

Deidentified data collected within this network and housed within cloud services, provisioned by NCATS, will become a resource for the greater rare disease research community and will be made available, via controlled access, to the scientific community, stakeholders and other relevant partners in a manner that meets all NIH human subject's protection, data safety and data sharing requirements.

Clinical Research Core

The investigative team of the Clinical Research Core will serve as a network resource that consults with RDCRCs to provide guidance on best practices that will facilitate clinical trial readiness. Areas of support should include protocol development and management, biostatistics, clinical research, trial designs and regulatory compliance. The investigative team will also support the RDCRC in establishing single IRBs and good data practices (FAIR principles) and will provide assistance in meeting required network data standards, developing database builds and SAS programming.

As many of the challenges faced by rare disease researchers are disease agnostic the investigative team of the Clinical Research Core will provide cutting edge information and guidance for RDCRN members on trans-RDCRN rare disease research issues (e.g., working with industry, identifying representative populations, and FDA interaction. They will also provide training on the use of all DMCC provided tools to appropriate RDCRC program staff. Such disease agnostic training opportunities should extend to participants of the investigative team of the RDCRC Career Enhancement Core.

To facilitate communication and collaboration within RDCRC, the investigative team of the DMCC Clinical Research Core will provide an internal website, or "Members Landing Page," for the day-to-day programmatic needs of each RDCRC.

The investigative team of the Data Management Core will coordinate resources including but not limited to the RDCRN Protocol Index, a comprehensive database of all RDCRN research protocols supported by the projects funded.

The investigative team of the Data Management Core will continue to manage the RDCRN Contact Registry which supports the dissemination of information from the RDCRN to the but, also offers participants from the broader rare diseases community an opportunity to participate in research.

In order to monitor clinical trial readiness, the investigative team will develop and utilize clinical trial readiness metrics for both regulatory requirements (e.g., protocols, IRBs) and clinical research components (e.g., natural history studies, outcome measures, biomarkers) to aid RDCRC in evaluating their progress in clinical trial readiness.

Engagement and Dissemination Core:

The primary goal of the investigative team of the Engagement and Dissemination Core is to promote patient engagement and broad dissemination of research conducted within the network. By working collaboratively with the RDCRCs and the patient advocacy groups, the investigative team of the Engagement and Dissemination Core will develop a broad RDCRN outreach plan for the network and its RDCRC. The outreach will extend to basic and clinical researchers, academic and practicing physicians, patients, industry, other rare disease research networks and the general public.

Special emphasis will be placed on outreach to diverse and underrepresented groups to promote diversity in rare disease research.

The investigative team will provide resources to the network including but not limited to:

• An internet-based web-portal to serve as a central access point to information generated by the RDCRN.
• An internet-based website for each RDCRC.
• Social media to share highlights of the RDCRC research, researchers and patient advocacy groups.

The investigative team of the core will also coordinate trans-RDCRN activities and educational opportunities for individuals participating in the Career Enhancement Cores of the participating RDCRCs. Activities/Opportunities should be disease agnostic and beneficial and informative to any early career rare disease researcher.

The investigative team of the core will have the primary responsibility for providing guidance and support to the patient advocacy groups. Activities that are encouraged include educational opportunities and coordination of activities related to rare disease research.

The investigative team of the Engagement and Dissemination Core will collaborate with the Data Management Core to curate a collection of shared resources for use by RDCRN members (e.g., webinars, templates, processes).

Governance

RDCRN Governance (Network-specific)

The awards funded under this NOFO will be cooperative agreements (see Section VI.2. Cooperative Agreement Terms and Conditions of Award).

The RDCRN will consist of all the awarded RDCRCs, their affiliated patient advocacy group(s), the DMCC, and NIH program representatives. The RDCRN governance consists of the NCATS RDCRN Program Director, JLT, Network SC, and the CPAG SC.

NCATS RDCRN Program Director

• Provide coordination for network activities.
• In consultation with NIH staff, other federal agency staff, and non-NIH experts in the field, provide feedback and guidance on program activities.
• Coordinate with the DMCC to interact with PD(s)/PI(s) on a regular basis to facilitate access to NIH resources.
• Help organize the annual Network SC Meeting.
• Help coordinate collaborative efforts within the RDCRN.
• Help facilitate collaborative efforts with external partners (e.g., National Organization for Rare Disorders (NORD), European Rare Disease Research Coordination and Support Action consortium (ERICA), Chan Zuckerberg Initiative (CZI)).
• Be the vote casting NIH member of the Network SC (the NIH will have only one vote – that will be a consensus decision across PO).
• Advise the SC on drafting and applying operating policies that require coordinated action across the RDCRN.
• Work collaboratively with all PO and PS.
• Have responsibility for negotiating and approving RDCRN milestones that are quantifiable for measuring success in meeting the goals of RDCRN membership. Each RDCRN milestone should have quantitative criteria associated with them.

RDCRN Joint Leadership Team
The RDCRN JLT will serve as the Executive Committee of the RDCRN. The JLT will meet on a monthly basis to hold strategic discussions regarding the RDCRN functioning and will make executive decisions related to RDCRN activities. The JLT will screen any potential cross-network research projects from external or internal collaborators and make recommendations to the Network SC. In addition, the JLT will discuss any issues in need of consensus or resolution and will identify solutions to be discussed with the RDCRN SC and/or the CPAG SC. 
 

The JLT is composed of:

• Network SC Chairs
• CPAG SC Chairs
• One DMCC PD/PI representative
• NCATS RDCRN Program Director

RDCRN Network Steering Committee
The Network SC will identify scientific and policy issues that need to be addressed at the network level and review and approve all RDCRN-wide policies. The Network SC will identify broad issues in the field of rare diseases research that can be addressed by the network. It will also ensure dissemination of program data, career enhancement schedules and other materials to the wider scientific community. The Network SC may establish subcommittees and working groups to facilitate development, implementation, and monitoring of specific network functions as needed.

The Network SC is composed of:

• The RDCRC PD(s)/PI(s)
• CPAG SC Chairs
• The PD(s)/PI(s) of the DMCC
• NCATS RDCRN Program Director
• NIH PO(s)/PS(s) from participating ICOs

RDCRN Coalition of Patient Advocacy Group Steering Committee
The CPAG SC will identify scientific and policy issues that need to be addressed at the network level, as well as broad issues in the field of rare diseases research that are specifically relevant to patients.

The CPAG SC is composed of:

• One patient advocacy group representative from each RDCRC
• Two PD(s)/PI(s) representatives
• The PD(s)/PI(s) of the DMCC
• NCATS RDCRN Program Director
• NIH PO(s)/PS(s) from participating ICO
• RDCRN Governance (network-specific)

DMCC Governance
The PD(s)/PI(s) of the DMCC will serve as the Core Lead(s) for the Administrative Core. The DMCC PD(s)/PI(s) should develop and maintain an environment that fosters collaboration that will provide support to the RDCRCs' patient-oriented, multi-site, multi-disciplinary research collaborations and training. The DMCC PD(s)/PI(s) cannot serve as the PD/PI Investigator of a project in another active RDCRN award.

The DMCC will establish an External Advisory Committee (EAC) consisting of scientific, clinical and patient group representation that will be composed of at least five members. The EAC serves in an advisory capacity to the DMCC by providing an annual review and critique of progress of the DMCC. The EAC must meet in-person or virtually at least once a year, beginning in the first or second year of the award.

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

Only the following applicant may apply for this single source funding: Cincinnati Children's Hospital Medical Center (CCHMC). Please refer to Section I Notice of Funding Opportunity Information for more details.

Non-domestic (non-U.S.) Entities (Foreign Organization) 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 his/her 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. 

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.

Only a single award will be issued to the Cincinnati Childrens Hospital Medical Center under this single source funding opportunity. Please refer to Section I. Notice of Funding Opportunity Information for more details.

Applicants must demonstrate experience administering a large data management and coordinating center, working in a cloud environment, and having a strong understanding of the special research needs of rare disease researchers. Applicants must demonstrate significant experience with coordinating collaborative clinical research. The DMCC PD(s)/PI(s) cannot serve as the PD/PI of a project in another active RDCRN award at the time of award. The minimum effort of the PD(s)/PI(s) across DMCC cores should be at least 2.0 person months per year. If there are multiple PDs/PIs each individual must meet the minimum requirement.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2- Definitions 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 or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

NCATS Letters of Intent
Telephone: 301-827-9549
Email: [email protected] 

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

The application should consist of one each of the following components:

• Overall: Required
• Administrative Core: Required
• Data Management Core: Required
• Clinical Research Core: Required
• Engagement and Dissemination Core: Required

Overall Component

When preparing the application, use Component Type ‘Overall’.

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

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Other attachment:

Transition Plan (Required)

The applicant must propose a transition plan that outlines the methods and timelines for the smooth transfer of the critical functions of each core to another award recipient should funding not be continued in the future.

The transition plan attachment may be no more than 3 pages in length.

Information must include, but is not limited to, a description and timeline to:

• Provide a complete inventory of any systems that have been deployed in the cloud environment.
• Provide REDCap/box instances and transfer the instance of Complion.
• Demonstrate how tools developed, or deployed in the cloud are utilized.
• Share any instances of custom tools and how they function within the DMCC cloud environment.
• Provide information and access to all external and internally facing websites.
• Provide information and access to resources from each DMCC core that is necessary to maintain support and functionality of the RDCRN.
• Provide Standard Operating Procedures (SOPs) for each core that can be shared with new recipients.
• Provide all documentation to NCATS.
• Provide all DMCC structure and management controls to NCATS.
• Provide active data sharing agreements upon termination and transition of the award.

Applications missing the transition plan may be deemed incomplete and not sent forward for review.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Describe the overall goals of the DMCC for the proposed performance period of the application. Describe the objectives of the center for facilitating clinical trial readiness. Also describe the center's objectives for providing clinical research and data management for the RDCRCs, coordinating RDCRN-wide activities, and serving as a conduit of RDCRN-related information to both the research community and the general public.    

Research Strategy:

The Overall Research Strategy should describe the DMCC, its goals and objectives, background information, the overall importance of the program in establishing the RDCRN as a data management and coordinating center and as a resource for rare disease researchers, patients, stakeholders, clinicians and the general public. Describe the rationale for the overall proposed program. Explain the strategy for achieving the goals defined for the overall program and how each core the investigative team of the relates to that strategy. A successful grant application will include a well-integrated strategy that clearly shows how the investigative team of the cores will foster clinical trial readiness and how the DMCC will serve as a resource for the greater rare disease research community. It will also describe how data will be made available to the scientific community, patients, stakeholders and other relevant partners in a manner that meets all NIH human subject's protection, data safety and data sharing requirements, as appropriate and consistent with achieving the goals of the program. A description of how the NCATS ITRB Cloud Computing Services and Engineering support will be used to achieve the mission of the DMCC must be included.

The DMCC should be viewed as interrelated cores that provide support to individual RDCRCs, to the network as a whole, and to the greater rare diseases research community. Because each core should be strong individually and complementary to the other cores and the RDCRN, it is important to describe the synergy across cores. Provide justification in the application that key personnel will collaborate effectively. Describe the organizational structure of the DMCC including the cores. Explain how different components of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goals of the RDCRN, and how combined resources create capabilities that are more than the sum of the parts. Describe how patients and stakeholders are meaningfully incorporated into DMCC activities. Describe workflow plans and timelines. It is especially important to provide timelines and standard operating procedures (SOPs) for onboarding any new RDCRC that are funded during this cycle and providing support for RDCRC that are transitioning off the RDCRN.

Letters of Support:

Applicants must provide letters from the appropriate high-ranking institutional official(s) from the lead institution and partnering institutions that:

• Commit the institution(s) to the DMCC goals, indicating that the program will be integral to their broad vision of clinical research in rare diseases.
• Defines the position, authority, and reporting responsibility (on the institution's organizational chart) for the DMCC PD(s)/PI(s).
• Defines the financial and other resource support for the DMCC that will be provided by the applicant institution(s). There are no dollar requirements, but specific commitment is required. Some examples include financial support, adequate space, release time agreements, tenured or tenure-track positions for clinical/translational faculty, FTEs for clinical support or ancillary personnel, core consolidation, and maintenance. Specific commitments to cores and other components can be summarized in a table.
• Defines the authority or influence that the DMCC PD(s)/PI(s) has, and/or will have over the different components of the DMCC, facilities and space, as well as decision-making authority for hiring and/or approving new faculty and support personnel.

Applicants may provide letters of support specific to the cores if they do not duplicate other letters of support. Please label each core-specific letters of support with the subcomponent it is supporting.

Also, only include letters of collaboration from individuals and groups who will contribute in a substantive, meaningful way to the scientific development or execution of the overall DMCC, whether or not salaries are requested. Supporting letters from patient or stakeholder groups may be included.

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.

Other Plan(s): 

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

• This NOFO funding is not intended to generate scientific data itself but to support scientific data generated under the funding NOFO PAR-24-206. A DMS Plan is not applicable to this specific NOFO. DMS Plans will be submitted for scientific data generated under the other applicable funding NOFO (PAR-24-206).

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

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.

PHS Assignment Request Form (Overall)

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

Administrative Core

When preparing your application, use Component Type ‘Admin Core.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Administrative Core

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Administrative Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Administrative Core)

Budget forms appropriate for the specific component will be included in the application package.

The Administrative Core budget should include budget for planning and conducting at least one face to meeting for the RDCRN network in the greater Washington DC metropolitan area.  They should also budget for travel for the RDCRC PD(s)/PI(s), along with support staff needed to manage the meeting,

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Administrative Core)

Specific Aims: Describe the goals of the Administrative Core and how these goals will contribute to substantial and sustained support of the DMCC and, as a result, the RDCRN. The specific aims should address plans for communication and coordination across cores, the RDCRN and the CPAG.     

Research Strategy: 

The investigative team of the Administrative Core will be responsible for the management and administration of the DMCC. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program.

This section of the application should describe the strategies and processes that will be used to manage the DMCC and achieve the goals of both the DMCC and the overall RDCRN. A narrative should be provided that describes how the investigative team of the Administrative Core will provide overall coordination and management of RDCRN activities including:

• RDCRN SC
• RDCRN JLT
• CPAG activities
• Bi-annual RDCRN Network-wide meetings
• Manage working group meetings
• Oversight and the coordination of activities across all DMCC cores
• Maintaining and disseminating the Network Operations Manual that defines roles, responsibilities, minimum network standards, and operational requirements for all RDCRN participants.
• They will also be responsible for preparing an RDCRN-wide annual report to be made publicly available.

Describe how an EAC consisting of scientific, clinical and patient group representation that will be composed of at least five members will be established and will function. Those applicants with established EAC members should include their continued commitment in Letters of Support.

Describe how the investigative team of the Administrative Core will work collaboratively with the Data Management Core to:

• Track all research projects and career enhancement program beneficiaries.
• Develop a plan and timeline for both onboarding RDCRC new to the network and transitioning groups that will complete their funding eligibility and rotate off the RDCRN at the end of the funding cycle.     

Letters of Support: Any letters of support should be included in the Overall Component.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 SF424 (R&R) Application Guide must be followed.

Data Management Core

When preparing your application, use Component Type ‘Data Management Core.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Data Management Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Data Management Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Management Core

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Data Management Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Data Management Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Data Management Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Management Core)

Specific Aims: Describe the specific aims of the Data Management Core and how these goals will facilitate the development of a management system for the collection, storage and quality control of data; promote the use of data standards; and provide a portal for data use and sharing, as appropriate and consistent with achieving the goals of the program. The aims should address not only the delivery of services or materials, but also the processes for ensuring the consistent quality of the services or materials, fair access by users and efficient use of the resources.   

Research Strategy:

Describe the function of the core as a resource for the program. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program.

This section must clearly present the facilities, techniques, and professional skills that the core will provide. Describe the role of the core as a resource to the RDCRN. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program. Describe how the NCATS ITRB Cloud Computing Services and Engineering support will be used to achieve the goals of the Data Management Core.

Describe how the Data Management Core, in collaboration with the Engagement and Dissemination Core, will provide:

• A management system for the collection and storage of data.
• A plan for maintaining confidentiality and addressing privacy issues.
• An easily accessible portal and tools for RDCRN members to independently access and download data sets for analysis.
• Remote data auditing

Describe how the Data Management Core will support and enhance a collaborative informatics community for the RDCRN Program by:

• Establishing a Good Data Practices work group with representatives from each RDCRC.
• Facilitating the use of CDE.
• Establishing processes and methods for common IT architecture for the RDCRN Program Consortium including defining technical standards, identifying security requirements, and identifying and integrating existing resources.
• Leveraging innovative new resources including those developed by other NIH supported initiatives (e.g., CTSA Program Data to Health [CD2H]) .
• Promoting the use of clinical and research data that are machine readable and that adhere to the FAIR (findable, accessible, interoperable, and re-useable) principles.
• Developing and implementing standard uniform protocols for data collection (e.g., CDE), as well as specimen tracking in individual and multi-center Consortium studies.

Data Sharing under this NOFO is expected to be handled to increase the value of the significant public investment in the creation and operation of the network. Consistent with achieving the goals of the program, Although no Data Sharing Management Plan is required, NIH expects that applicants  should address how they will ensure how datasets from the RDCRN will be widely shared with the scientific community for research, while carefully observing standards of patient privacy, confidentiality, and management of health information. Information such as study protocols, descriptions, bioinformatics tools, and publications are expected to be made available through an open access section of a database such as the RDCRN and other public web sites, and publication in the scientific literature. Describe how the afore-mentioned issues will be addressed while providing optimal data sharing.    

Letters of Support: Any letters of support should be included in the Overall Component.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided  in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

PHS Human Subjects and Clinical Trials Information (Data Management Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 SF424 (R&R) Application Guide must be followed

Clinical Research Core

When preparing your application, use Component Type ‘Clinical Rsrch Core."

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Clinical Research Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Clinical Research Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Research Core

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Clinical Research Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Clinical Research Core

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Clinical Research Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Clinical Research Core)

Specific Aims: Describe the specific aims of the Clinical Research Core and how these goals will facilitate the development of clinical trial readiness within the RDCRN. The aims should address not only the delivery of services or materials, but also the processes for ensuring the consistent quality of the services or materials, fair access by users and efficient use of the resources.   

Research Strategy:

Describe the role of the core as a resource for the RDCRN as a whole. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program.

Describe the function of the Clinical Research Core as a resource to the program. This section must clearly present the facilities, techniques, and professional skills that the core will provide. Describe the function of the core as a resource to the program. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program. Describe the Clinical Research Core's ability to provide expert consulting and support for:

• Protocol Development and Review
• Protocol Management
• Biostatistics
• Study designs
• Single IRB
• Standard Operating Procedures
• Form development

Describe the synergy and expertise of the team as a whole to provide information, guidance and training for issues including, but not limited to, navigating the regulatory process, working with industry or leveraging other NIH sponsored programs (e.g., Therapeutics for Rare and Neglected Diseases [TRND] or Trial Innovation Network) that will foster appropriate communication among RDCRCs and other relevant participants in the drug development pipeline. Applicants should not duplicate individual expertise that belongs in the biographical sketches.

While each RDCRC will have its own rare disease specific career enhancement program describe how the Clinical Research Core will provide trans-RDCRN career enhancement opportunities to RDCRC student(s)/scholars that is disease agnostic and promotes best practices in clinical trial readiness.

The DMCC will provide consulting services to the RDCRCs to assist in establishing a single IRB for Multisite projects.

Letters of Support: Any letters of support should be included in the Overall Component.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

PHS Human Subjects and Clinical Trials Information (Clinical Research Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 SF424 (R&R) Application Guide must be followed.

Engagement and Dissemination Core

When preparing your application, use Component Type ‘Engmnt Dsmntion Core.’

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Engagement and Dissemination Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Engagement and Dissemination Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Engagement and Dissemination Core)

Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Engagement and Dissemination Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Engagement and Dissemination Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   

Budget (Engagement and Dissemination Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Engagement and Dissemination Core)

Specific Aims: Describe the specific aims of the Engagement and Dissemination Core and how these goals will facilitate a broad outreach plan for the RDCRN. The aims should describe outreach to basic and clinical researchers, academic and practicing physicians, patients, stakeholders and the general public. The aims should address not only the delivery of services or materials, but also the processes for ensuring the consistent quality of the services or materials, fair access by users and efficient use of the resources.   

Research Strategy:

Describe the role of the core as a resource. Describe the function of the Engagement and Dissemination Core as a resource for the RDCRN as well as the Rare Diseases Research Community as a whole. This section must clearly present the facilities, techniques, and professional skills that the core will provide. Discuss ways in which these centralized services will produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program.

Describe how the Engagement and Dissemination Core will develop a robust Promotion and Outreach plan for the RDCRN that details interactions with key partners, beyond patients and stakeholders, that include other rare diseases experts, related NIH programs, the greater biomedical research community, NIH staff, journal editors, professional societies, and industry, to meet the goals of the Program, including data sharing.

Describe how the Engagement and Dissemination Core will facilitate collaborations among key stakeholders to further the application of research findings from the RDCRN. Describe how the DMCC will utilize the NCATS ITRB Cloud Computing Services and Engineering support to achieve the Center's goals.

Describe how the Engagement and Dissemination Core, in collaboration with the Data Management Core, will provide a secure internet-based infrastructure (web-portal or other method) to support communications, and document and resource sharing with sources both internal and external to the RDCRN.

Describe how the accomplishments, resources, policies and best practices of the RDCRN will be shared with the patient advocacy groups as well as the general public. Also describe how scientific information will be shared in plain language to provide greater access to the information.    

Describe how the patient advocacy groups will be integrated into the RDCRN program.

Letters of Support: Any letters of support should be included in the Overall Component.

Resource Sharing Plan:

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

PHS Human Subjects and Clinical Trials Information (Engagement and Dissemination Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 SF424 (R&R) 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

4. Submission Dates and Times

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) using ASSIST or other electronic submission systems. 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 How to Apply- Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

For information on how applications will be automatically assembled for review and funding consideration after submission, refer to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 How to Apply - Application Guide. 

See more tips for avoiding common errors.

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

In order to expedite review, applicants are requested to notify the NCATS Referral Office by email at [email protected]  when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions 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 NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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).

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 Center address the needs of the research network that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network?

Specific to this NOFO:

As it relates to the DMCC’s relationship to the RDCRN network, to what extent will the proposed DMCC address the needs of both the individual RDCRC and the RDCRN as a whole? To what extent are the scope of activities proposed for the DMCC and its cores, appropriate to meet those needs? To what extent will the DMCC bring unique advantages or capabilities to the RDCRN and the greater rare disease research areas?        

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing rare disease research? Do the investigators demonstrate significant experience with coordinating collaborativeresearch? 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 Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this NOFO: 

To what extent do the PD(s)/PI(s) and other personnel have demonstrated experience administering a large data management and coordinating center, working in a cloud environment, and having a strong understanding of the special research needs of rare disease researchers.? To what extent is there a feasible succession plan within their Leadership plan?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network the Center 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?

Specific to this NOFO:

To what extent does the overall vision and conceptual framework for the DMCC present a novel approach to coordinating rare disease research?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? 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?

Specific to this NOFO:

To what extent is the approach taken by the DMCC likely to be successful; with each of the cores not only individually meritorious but also complementary to the other components, and related to the overall RDCRN? Are there appropriate plans for the DMCC to collaborate and otherwise contribute to the broader rare disease research community? To what extent does the DMCC have a clear vision for establishing an identity for the RDCRN as a rare diseases research resource? To what degree do the centralized services produce an economy of effort and/or savings in overall costs compared to their inclusion as part of each project in the program? To what extent are patients and stakeholders involved in DMCC activities in a meaningful manner?

Assess 1) the adequacy of the plans for how the applicant and the institution will continue to support studies already underway in the network without significant disruption, and 2) whether eventual transition to a new DMCC could occur without significant disruption.

If the DMCC manages data from human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed? 

Environment

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

Specific to this NOFO:

To what extent does the institutional leadership commit to supporting the DMCC?  To what extent is the institutional commitment appropriate for supporting a DMCC which will be supporting the whole Rare Disease Clinical Research Network? 

Review Criteria - Cores

Reviewers will provide overall numeric scores reflecting the merit of the individual cores based on criteria below.

Review Criteria for the Administrative Core

• To what extent are the skills of the proposed investigative team of the Administrative Core sufficient to meet the described requirements?
• To what extent are the proposed strategies and processes that will be used to manage the DMCC appropriate for scientific administration as well as fiscal administration, procurement, property and personnel management, planning, budgeting etc.?
• To what extent is the DMCC structure sufficient, including its internal and external procedures for managing the activities of the DMCC and the RDCRN?
• To what extent are there appropriate plans for establishing the EAC, and are there appropriate plans for the EAC to serve in an advisory capacity for the whole DMCC?
• To what extent does the Director(s) have the leadership and research qualifications to lead the Administrative Core?
• To what extent is there an appropriate plan for establishing and maintaining effective communication and cooperation among the DMCC cores? With RDCRC sites? As a network as a whole?
• Is there meaningful engagement with patient or stakeholder groups?
• Is the environment for the Administrative Core adequate and appropriate to support the overall DMCC?  Is there evidence of institutional support for the management of the DMCC?
• To what extent does the External Advisory Board have the needed expertise to serve in an advisory capacity for the DMCC?
• To what extent is the investigative team of the Administrative Core working collaboratively with the Data Management Core to manage tracking of network activities?
• To what extent is the plan for onboarding new RDCRC and managing exiting RDCRC sufficient for meeting the needs of the RDCRCs?
• To what degree will the Administrative Core and the Data Management Core manage information relating to research projects and career enhancement program beneficiaries? To what extent is the timeline realistic and appropriate to facilitate onboarding and transitioning RDCRCs?

Review Criteria for the Data Management Core

• To what extent are the core activities capable of effectively and efficiently supporting research productivity?
• To what degree is the plan for oversight and prioritization of user requests for core services adequate and fair?
• To what extent does the core provide adequate leadership and technical expertise to ensure that it meets its stated goals?
• To what extent are the staffing, allocated space, equipment, and other resources that are available to the core sufficient to meet the anticipated demand for its services?
• To what extent will the services provided facilitate clinical trial readiness?
• To what extent does the plan provide provisions for diverse programmatic needs and capabilities of the RDCRCs?
• To what extent is the plan for data to be made available for RDCRN participants, the broad research community and patients and/or stakeholders appropriate?
• To what degree is there meaningful inclusion of patients or stakeholders?

Review Criteria for the Clinical Research Core

• To what extent are the core activities capable of effectively and efficiently supporting research productivity?
• To what extent is the plan for oversight and prioritization of user requests for core service adequate and fair?
• To what extent does the core provide adequate leadership and technical expertise to ensure that it meets its stated goals?
• To what extent is the staffing, allocated space, equipment and other resources that are available to the core sufficient to meet the anticipated demand for its services?
• To what extent will the services provided facilitate clinical trial readiness?
• To what extent does the plan provide provisions for diverse programmatic needs of the various RDCRCs?
• To what extent is there a plan to provide career enhancement on issues that are relevant to all RDCRC sites at levels appropriate for both senior researchers as well as students/post-docs?
• To what extent is there meaningful engagement of patients or stakeholders in core activities?
• To what extent does the team demonstrate the expertise required to provide information, guidance and training for issues including navigating the regulatory process, working with industry, or leveraging other NIH sponsored programs?
• To what extent does the Clinical Research Core provide a career enhancement program that transcends individual RDCRC activities for the students/scholars including disease agnostic topics and best practices for clinical trial readiness?
• To what extent does the service provisioned support and facilitate independence for the RDCRC in developing single IRBs?                   

Review Criteria for the Engagement and Dissemination Core

• To what extent does the core provide adequate leadership and technical expertise to ensure that it meets its stated goals?
• To what extent is the  plan for interacting with RDCRCs and patient advocacy groups feasible?
• To what extent are the staff allocated sufficient to meet the anticipated demand on its services?
• To what extent is the outreach plan feasible and meaningful?
• To what extent does the plan or interacting with RDCRCs describe how accomplishments, resources, policies, best practices and scientific information will be shared with both the scientific community and the general public?
   
• Will information be shared in a timely manner?
• To what extent is the promotion and outreach plan effective for sharing RDCRN information broadly?
• To what extent is the plan to facilitate collaborations among key stakeholders appropriate and productive?
• To what extent is the plan to support communications using various modes effective?
• To what extent is the plan to share information both internally and externally to both lay and professional audiences effective?
• To what degree have the patient advocacy groups been integrated into the RDCRN program in a meaningful and productive manner?
• To what extent is there an appropriate and effective plan in place for a cross RDCRN program for participants in the Career Enhancement Cores of the RDCRCs? 

Additional Review Criteria - Overall

As applicable for the DMCC 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.

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/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

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

Revisions

Not Applicable.

Additional Review Considerations - Overall

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) (e.g., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

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 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access their 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

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. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

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

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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. 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, including of note, but not limited to:

• Federal-wide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

If a recipient receives and 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.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to System for Award Management (SAM.gov) requirements. SAM.gov requires Federal agencies to review and consider information about an applicant in the designated integrity and performance system (currently SAM.gov) prior to making an award. 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 addition to the information available in the responsibility/qualification records in SAM.gov, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at  75 and 2 CFR 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 award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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

• Defining objectives and approaches to plan, conduct, analyze, and publish results, interpretations, and conclusions of their activities.
• Serving as DMCC Director(s) and responsible for the integration and management of activities within the DMCC including ensuring data sharing and data use agreements are aligned with RDCRN requirements.
• Implementing a Local Executive Committee for day-to-day management of the DMCC, and an External Advisory Committee, with scientific, clinical and patient or stakeholder representation.
• Organizing and attending two RDCRN meetings per year (one in-person and one virtual).
• Organizing and attending monthly meetings for the RDCRN SC, RDCRN JLT, RDCRN CPAG SC.
• Coordinating and organizing networking wide activities (e.g., working group meetings, special seminars etc.).
• Collaborating with the RDCRCs to facilitate the use of network resources and promoting the use data standards.
• Actively collaborating and coordinating with the NCATS ITRB.
• Participating in the overall coordination of NIH research efforts in Rare Diseases including collaboration and consultation with other NIH recipients, the appropriate sharing of information, data, and research materials, and participating in NIH efforts to standardize and harmonize pre-clinical and clinical data collection.
• Establishing and implementing a transition plan based on the agreed upon timelines prior to the end of the project period.
• Retaining custody of and having primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.  

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The NIH Project Collaborator (PC) will:

• Oversee the activities of the DMCC to ensure activities are properly conducted and completed in a timely manner.
• Provide status updates on other RDCRN activities that may be relevant to the individual DMCC study goals or milestones.
• Monitor the operations of the DMCC for progress towards milestones and making recommendations on overall project directions.
• Inform the Network SC of any challenges or delays in project progress.
• Ensure proper collaboration between the DMCC and the other members of the RDCRN as well as the NCATS ITRB.
• Enlist additional technical experts as necessary from within the NIH, and other government agencies, to review scientific progress and administrative requirements to ensure compliance with NIH policies and procedures.

Additionally, the Project Collaborator, acting as the NIH Program Official, will be responsible for the normal stewardship of the award including the negotiation of the final set of approved DMCC award milestones.

Areas of Joint Responsibility include:

The RDCRN will consist of all the awarded RDCRCs, their affiliated patient advocacy groups, the DMCC, and NIH program representatives. All responsibilities are divided between recipients and NIH staff as described above.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: A designee of the Steering Committee 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 HHS 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. 

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.

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. 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.

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

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to  2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (Responsibility/Qualification in SAM.gov, formerly FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

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]

Tiina K. Urv, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-2746 
Email: [email protected] 

Jill A. Morris, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: [email protected]

Marilyn Moore-Hoon, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-9549 
Email: [email protected] 

Shannon Oden
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-594-3028 
Email: [email protected]

Chief Grants Management Officer
National Institute of Neurological Disorders and Stroke (NINDS)
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.