NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

The National Institute of Neurological Disorders and Stroke (NINDS) and the National Cancer Institute (NCI), with the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Sciences (NCATS), invite applications to continue Specialized Center - Cooperative Agreement (U54) awards made previously to RFA-TR-13-002 and RFA-OD-08-001 for research on rare diseases through participation in the Rare Diseases Clinical Research Network (RDCRN). This Funding Opportunity Announcement (FOA) is limited to those Program Directors/Principal Investigators (PD/PI) of Rare Diseases Clinical Research Consortia (RDCRC) who received an NINDS award under the Rare Diseases Clinical Research Network (RDCRN) program through RFA-TR-13-002 or an NCI award through RFA-OD-08-001.  The purpose of this limited competition FOA is to allow these NINDS- and NCI-awarded consortia an opportunity to compete to continue their participation in the RDCRN, which supports: 1) collaborative clinical research in rare diseases, including longitudinal studies of individuals with rare diseases, clinical studies, and/or clinical trials; 2) career development and advancement opportunities for clinical investigators in rare diseases research; 3) pilot/demonstration (proof of concept) clinical research projects; and 4) access to information related to rare diseases for basic and clinical researchers, physicians, healthcare professionals, patients, and the lay public.

Clinical data management for efficient data collection as well as data mining and data sharing will be addressed through the Data Management and Coordinating Center (DMCC) unit of the Rare Diseases Clinical Research Network (RDCRN).

Each RDCRC will perform collaborative multi-site clinical research in rare diseases, train new investigators in rare diseases research, and provide content for an internet resource site on rare diseases. Each RDCRC will consist of a consortium of clinical investigators, institutions, and relevant organizations, including patient advocacy group organizations and will focus on at least three related rare diseases, disorders or syndromes. Previous experience with the RDCRN has demonstrated that RDCRCs that both engage and integrate patient advocacy groups into their research program have achieved greater success in enrollment in studies. The RDCRC applicants at an institution with a Clinical and Translational Science Award (CTSA) are encouraged to use the resources available at their institution.

For this limited competition, the focus of each RDCRC application should be on rare neurological disorders (including at least three related diseases, disorders or syndromes) relevant to the interests and mission of the NINDS or on rare syndromes or disorders associated with oncologic disease relevant to the interests and mission of the NCI, and within scope of the eligible PD/PI's most recent RDCRC awarded grant.  Since rare diseases are diverse, the nature of clinical research that is feasible varies. The individual RDCRCs will be responsible for the design and implementation of their clinical studies. The Data Management and Coordinating Center (DMCC; see: https://grants.nih.gov/grants/guide/rfa-files/RFA-TR-13-003.html) for the RDCRN will provide the data management and support necessary for the RDCRCs to function optimally. The DMCC will work with each Consortium to integrate protocols, forms, and research tools into the Network. Each RDCRC will be responsible for its own biostatistical support and expertise for study design, protocol development, study implementation, and data analysis.

Approximately 25 million people in the United States are affected by an estimated 7,000 rare diseases or conditions leading to significant morbidity and mortality. 'Rare disease' is defined through an Amendment to the Orphan Drug Act of 1983 (Orphan Drug Act, P.L. 97-414; Health Promotion and Disease Prevention Amendments, P.L. 98-551) as a condition affecting fewer than 200,000 Americans or a disease with a greater prevalence but for which no reasonable expectation exists that the costs of developing or distributing a drug can be recovered from the sale of the drug in the United States.

In 1999, the NIH Office of Rare Diseases, now referred to as Office of Rare Diseases Research (ORDR) at the NCATS, convened a panel , comprised of academic scientists, representatives of voluntary patient support groups, pharmaceutical, biotechnology and device industries, and other Federal agencies. This panel made recommendations regarding the special research opportunities and health care issues posed by rare diseases. These recommendations encompassed four major areas: 1) stimulating research on rare diseases and conditions with specific emphasis on clinical research fostering the career development of  clinical research scientists in rare diseases, establishing diagnostic and treatment centers with informatics support, and promoting the collaboration of the voluntary patient support groups, health care systems, and industry; 2) utilizing research resources within the Clinical and Translational Science Awards (CTSAs), the development of a centralized information database containing research resources, made available to research investigators, physicians, and patients for their use; 3) coordination of rare diseases research and development activities, with a primary responsibility of ORDR to coordinate activities and act as a liaison between the rare diseases community and the NIH, including the public, and intramural and extramural investigators at the NIH Institutes and Centers (ICs) and other Federal agencies, manufacturers, and voluntary organizations; and 4) identifying emerging opportunities in rare diseases research, specifically through the establishment of specialized research and diagnostic centers to attract the interests of industry to promote advances and products for the prevention, diagnosis, and treatment of rare diseases. These recommendations are contained within the Department of Health and Human Services National Institutes of Health “Report on Steps to Coordinate Rare Diseases Research Programs," January 2001 (http://rarediseases.info.nih.gov/)

In November 2002, the Rare Diseases Act of 2002 (Public Law 107-280) directed ORDR at NIH to support regional centers of excellence for clinical research into, training in, and demonstration of diagnostic, prevention, and treatment methods for rare diseases. This law provides the legislated mandate for this FOA to address the needs of rare disease clinical research.

Investigations into rare diseases offer promising leads for scientific advancement. Many rare diseases represent single gene defects whose abnormalities in specific genes or proteins offer insight into normal biologic function. Other rare diseases are complex, resulting from the interaction of two or more genes. Understanding the pathogenesis of rare diseases may advance our understanding of more common medical disorders.

Despite the advances and opportunities for research in rare diseases, difficulties remain in clinical diagnosis, clinical trials methodology, and clinical management. Diagnoses may be straightforward as a result of well-described phenotypes or due to the availability of diagnostics tests, or conversely, they may be challenging due to a lack of well-defined diagnostic criteria. Furthermore, there are insufficient characterizations of the natural history of many rare diseases. Treatment can be equally challenging with many questions concerning clinical management and a lack of therapeutic options. Rare diseases pose unique challenges to identification and coordination of resources and expertise for small populations dispersed over wide geographic areas. Rare diseases research often requires collaboration of scientists from multiple disciplines sharing research resources and patient populations. Rigorous characterization and longitudinal assessment are needed to facilitate discovery of biomarkers of disease risk, disease activity, and response to therapy. In addition, systematic assessment could help to improve and develop an evidence base for current treatment strategies. Well described patient populations will be important to bring promising therapies to the clinic.

This initiative should facilitate therapy development and future clinical trials by identifying biomarkers for disease risk and disease severity/activity, clinical pharmacodynamic (PD) measures, and measures of clinical outcome.  It should encourage development of new approaches to diagnosis, prevention, and treatment of rare diseases.

The RDCRN consists of all funded RDCRCs and a single DMCC, and is intended to foster a collaborative and coordinated network of RDCRCs comprised of investigators at multiple institutions/sites and patient advocacy groups committed to the investigation of rare diseases working in partnership to enhance communication and sharing of resources in a multidisciplinary approach. The RDCRN focuses on the collection of clinical information to develop biomarkers and new approaches to diagnosis, prevention, and treatment and promote the career development of new clinical investigators in rare diseases research. The Network supports a comprehensive and integrated approach to data collection, storage, and management, and the integration of clinical data with other unique data, including genetic, imaging, pathologic, and laboratory data. This will incorporate new approaches to distributed computing and federated databases.

Each RDCRC within the Network consists of a consortium of clinical investigators, multiple institutions, and relevant organizations, including patient advocacy groups and will focus on at least three related rare diseases, disorders, conditions or syndromes that are relevant to the interests of the participating NIH ICs. The related rare disorders should fall within the interests and mission of the NINDS or NCI, and within the scope of the eligible PD/PI's most recently awarded RDCRC grant. The three diseases, disorders, conditions or syndromes proposed for inclusion in an RDCRC could be defined on the basis of differences in etiology (genetic, genomic, acquired), pathogenesis, affected molecular, biochemical, cellular, physiological features, or organ system involvement, natural history, distinguishing signs and symptoms and/or prognosis.  For example, disease-causing variants in the same gene leading to divergent phenotypes or variants in diverse genes leading to overlapping phenotypes could form the basis for a unified RDCRN application. Finally, successful applicants for RDCRCs are expected to synergize clinical research activities across diseases, so the thematic focus and rational basis for the diseases included should be both clear and compelling, and consistent with commonly accepted definitions of disease within the relevant biomedical research community.

Organization and Management of the Rare Diseases Clinical Research Network

A Steering Committee, composed at a minimum of the PD(s)/PI(s) of each RDCRC, the PD(s)/PI(s) of the DMCC, the chairperson of the Coalition of Patient Advocacy Groups (CPAG), and the NCATS, Office of Rare Diseases Research Program Coordinator for the RDCRN will establish the procedures for the function of the RDCRN, as outlined in Section VI. Awards Administration Information under "Network Steering Committee." Membership of CPAG will include all participating patient advocacy groups.

The DMCC for RDCRN has been established under another FOA (https://grants.nih.gov/grants/guide/rfa-files/RFA-TR-13-003.html). The DMCC will serve as a Network resource, working with and providing expertise for the RDCRCs. All RDCRCs are expected to work with the DMCC from the beginning to assure compatibility of data collection systems and consistent data standards. It will provide a scalable coordinated clinical data integration of developed and publicly available datasets for data mining at RDCRCs, web-based recruitment and referral, and a user-friendly resource site for the public. The DMCC will provide a management system for data collection, storage, as well as a portal and tools for research scientists and clinicians. In addition, the DMCC, in conjunction with the NIH, will provide logistical and administrative assistance for Network activities; produce and/or maintain Network Operating Policy and Procedures, documents, worksheets, and data collection forms; and monitor Network compliance while addressing privacy and confidentiality issues related to database management and multi-level data sharing. In order to participate in this Network each RDCRC is expected to use the DMCC supported by RDCRN for the above mentioned activities. To enhance recruitment in clinical studies each RDCRC is expected to utilize the Contact Registry developed by DMCC. The RDCRN Contact Registry is a method by which patients with rare diseases can register themselves with the RDCRN in order to be contacted in the future about clinical research opportunities and updates on the progress of the research projects. The contact registry is anonymous and free of charge. The Contact Registry can also be used by the investigators to facilitate the rapid enrollment of subjects in survey protocols. All RDCRCs will be expected to collaborate with the DMCC throughout the course of their study in order to assure compatibility and standardization of data management approaches.

The RDCRN will require cooperation among the NCATS, ORDR Program Coordinator for RDCRN, the participating IC Project Scientists, PD(s)/PI(s) of the RDCRC and their collaborators, and the PD(s)/PI(s) of the DMCC to maximize their effectiveness.

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

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education

• Private Institutions of Higher Education

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

• Hispanic-serving Institutions

• Historically Black Colleges and Universities (HBCUs)

• Tribally Controlled Colleges and Universities (TCCUs)

• Alaska Native and Native Hawaiian Serving Institutions

• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)

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

For-Profit Organizations

• Small Businesses

• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments

• County Governments

• City or Township Governments

• Special District Governments

• Indian/Native American Tribal Governments (Federally Recognized)

• Indian/Native American Tribal Governments (Other than Federally Recognized)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

Other

• Independent School Districts

• Public Housing Authorities/Indian Housing Authorities

• Native American Tribal Organizations (other than Federally recognized tribal governments)

• Faith-based or Community-based Organizations

• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• System for Award Management (SAM) (formerly CCR) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.

• Grants.gov – Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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 underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

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

This Funding Opportunity Announcement (FOA) is limited to those Program Director(s)/Principal Investigator(s) of Rare Diseases Clinical Research Consortia (RDCRC) who received an NINDS award under the Rare Diseases Clinical Research Network (RDCRN) program through RFA-TR-13-002 or an NCI award through RFA-OD-08-001.  

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

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.  This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.

• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

• Of an application with a changed grant activity code.

Applicants can access the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.

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 for NINDS applications should be sent to:

Laura A. Mamounas, Ph.D.
Telephone: 301-496-5745

Fax: 301-402-1501
Email: mamounal@ninds.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for RDCRC Administrative Core)	6
Project (use Clinical Research Projects for Observational/Longitudinal Studies; Pilot/Demonstration Project Clinical Research Program; Career Development and Advancement Project.)	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required

• RDCRC Administrative Core: required

• Clinical Research Projects (for Observational/Longitudinal Studies): at least two Projects are required, one of which must be a longitudinal study

• Pilot/Demonstration Project Clinical Research Program: required

• Career Development and Advancement Project: required  

When preparing your application in ASSIST, use Component Type ‘Overall’.

All instructions in the SF424 (R&R) 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 with the following exceptions:

Facilities and Other Resources: Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated institutions and units, rare diseases patient populations (also discussed below), geographic distribution of space and personnel, and consultative resources. Each RDCRC must provide biostatistical support. Describe institutional capability for statistical and clinical support. The RDCRC applicants at an institution with a Clinical and Translational Science Award (CTSA) are encouraged to use the resources available at their CTSA institution.

Provide a statement that addresses how the institutional commitment will be established and sustained, and how the RDCRC research effort will be given a high priority within the institution. The institutional commitment may be in the form of support for recruitment of scientific talent, provision of discretionary resources to the RDCRC Director, assignment of research space, cost sharing of resources, protected time for the investigators to pursue clinical research and mitigate the demands of providing patient care, and/or other ways proposed by the applicant institution. The primary institution is strongly encouraged to demonstrate its commitment to the RDCRC by providing financial support to the career development and pilot/demonstration clinical research projects on an awarded RDCRC, as well as other programmatic needs identified as high priority.

Project/Performance Site Location(s) (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 & Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) 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 applications, an Introduction to Application is required for the Overall component  

Specific Aims: Describe specific aims of the RDCRC.  

Research Strategy: Briefly describe the overall proposed clinical research program of the RDCRC indicating the goals and objectives of the individual clinical research projects.  In addition, the following items should specifically be addressed in this section:

1. RDCRC Program Overview and Statement of Objectives

Describe the group of rare diseases to be included, the rationale for this grouping, and the relevant expertise available in the consortium. Each RDCRC should include a group of at least three related rare diseases, disorders or syndromes. State the clinical research objectives of the proposed RDCRC and the research focus of the application. Describe the rationale for the proposed clinical research program on the proposed group of diseases, and explain the strategy for achieving the objectives of the overall program, how each project relates to the strategy, and how the diseases relate to one another. Briefly describe the clinical research projects and the rationale for each within the RDCRC.

2. Multidisciplinary Team Involving Patient Advocacy Groups and collaborations

Describe the nature of the multidisciplinary team and approach for the consortium of clinical investigators, institutions, and relevant organizations, including patient advocacy groups, focused on a subgroup of at least three rare diseases. Include a plan to fully incorporate the Patient Advocacy Groups’ representation in the organizational structure and consortium interactions (conference calls, meetings, etc.). Describe the role of the patient advocacy group(s) and other relevant organizations in consortium activities including their level of  participation across the planned objectives (e.g., in addressing clinical design, recruitment, and education). The proposed patient support organization’s activities should be appropriate for the level of advocacy capabilities.

It is important to indicate prior collaborative arrangements between investigators in the group and patient advocacy groups, to emphasize the events that have led to the current application, and to predict the anticipated unique advantages that the research within the proposed RDCRC would gain. Identify how the collaboration(s) with the scientific community and patient advocacy groups will help to advance the proposed research aims.

Applicants should provide evidence that the RDCRC functioned collaboratively as the result of a team approach which included active PAG participation in the prior funding period.  Provide examples of previous and/or ongoing collaborations (including sharing data and resources with other sites in the Network, participating in working groups or committees, collaborating on activities of mutual interest with the other participating RDCRCs, PAGs, and with the NIH, etc.).

3. Website for Education and Research

Each application must include a description of materials to be included in a web site for education and research in rare diseases. These  materials should include a description of resources for lay public, patients, basic and clinical researchers, and clinicians. Examples include but are not limited to: patient registries; contacts for animal models; tissue, serum, specimens, DNA, etc.; antibodies and research reagents; genetic resources; registries; education materials; and/or diagnostic flow charts. Do not include URLs within the application itself; reviewers will be instructed not to visit external links during their review of the application.  The actual design and implementation of the site will be a collaborative activity of the DMCC and all RDCRC through the Steering Committee. The RDCRC and DMCC must agree to work cooperatively to develop the web site resource and provide content related to its focused rare diseases. Institutional and outside support for this program is encouraged.

4. Rare Diseases Patient Population

Each RDCRC must document access to a sufficient patient population in the rare diseases focus of the application and provide reasonable assurance that the patients and human specimens needed for clinical research are readily available. Each RDCRC must describe in detail how patients will be identified and recruited for study. Resources for outreach, recruitment and retention of these patients should be provided.   Provide an overview of the statistical and clinical support available to the RDCRC to study rare diseases patient populations.

5. Progress during prior funding period

Document what projects from the prior funding period have been completed and how these projects have helped to advance the field. Include publications relevant to the RDCRC project, and other forms of information dissemination used to communicate with the scientific community.  Applicants should indicate if the enrollment targets were reached and provide clear documentation of having accomplished the recruitment goals in the prior funding period(s).   

6. Plan for Streamlining Protocol Approval Process

It is advantageous for clinical studies of diseases in small populations to use a multi-centered approach.  However, this requires approvals from multiple IRBs, which prolongs the protocol approval process and delays patient recruitment.  Moreover, there are other regulatory requirements when participating centers are in different countries and additional approvals are necessary from the RDCRN and NIH.  Applicants should present a plan for how the proposed RDCRC will try to streamline the protocol approval process.  Specifically, applicants are strongly encouraged to consider models that will facilitate “shared review” such as IRB Share or a central IRB of record for multisite studies and provide plans for implementation.  Having a central IRB of record for multisite trials is preferred and may even improve subject safety and scientific validity, as well as trial efficiency.  The central IRB might logically reside at the RDCRC PD/PI’s institution.   Member institutions of the consortium would agree to a) accept the findings of the central IRB, b) accept the central IRB findings with modifications, or c) convene their own IRB.  If a central IRB or IRB Share is not feasible, applicants should discuss systems for making the protocol approval process as rapid and efficient as possible.

Letters of Support: Letters from high-level institution official(s) (e.g., Dean of the School of Medicine, President and Vice President for Research) should be included confirming commitment to the RDCRC. For the consortium, the institution that submits the U54 application must receive a formal written agreement(s) from the other participant organization(s), including patient advocacy group(s), and submit them with application. This agreement should clearly delineate the institutional commitment of the participating organization(s) (in the ways outlined above) to the RDCRC Program.  Provide documentation for established consortium agreement with other institution(s) to provide adequate access to clinical specimens (e.g., tissues, blood, and urine) and/or patients at another site(s).  Supporting letters from collaborating patient advocacy groups are strongly recommended.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Applications for RDCRC cooperative agreement awards are expected to include a data and research resources sharing plan that covers the entire application including all project and core components. The plan should outline how final research data will be shared by the members of individual RDCRC, as well as with the research community at large, or state why this is not possible.

• The NIH also encourages the timely sharing of biomedical resources  by awardees. Therefore, the plan should also describe how unique research resources will be distributed, e.g., through the institution, a repository, dbGAP, or national coordinating center. During the 5-year funding period, if a RDCRC proposes to collect biospecimens, the RDCRC is expected to register contact information regarding its Biorepository with the Biospecimen/Biorepositories Website RD-HuB (http://biospecimens.ordr.info.nih.gov/). RDCRCs are also encouraged to upload information about their biospecimen into the RD-HuB specimen locator on this website to help researchers utilize available specimens.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

When preparing your application in ASSIST, 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 (RDCRC 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 (RDCRC Administrative Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (RDCRC 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) (RDCRC 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 (RDCRC Administrative Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Core 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. 

• The RDCRC Administrative Unit must include an Administrative Director who will be responsible for assisting the RDCRC Director (PD/PI of the application) with the day-to-day administrative details, program coordination, and planning and evaluation of the program, and who would be in charge in the absence of the RDCRC Director.

• The Administrative Director may be from a different Institution but must be a clinical investigator who ensures a mutually supportive interaction between scientists conducting clinical research. The qualifications of the clinical investigator  should be described.

Budget (RDCRC Administrative Core)

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

The RDCRC Director (PD/PI of the application) is expected to make a commitment of at least 2.0 months to the overall administration of the program plus 1.2 months as a leader of a RDCRC project (if leading a clinical research project). RDCRC Administrative Unit support personnel may be budgeted at no more than 12 calendar months, which may be divided among one or more positions. This FTE must be fully justified. Note that the RDCRC Director is expected to send two RDCRC participants to biannual meetings in the Washington, D.C. or Bethesda MD area, and should budget for these meetings.

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          (RDCRC Administrative Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is required for the Administrative Core.  

Specific Aims: Describe specific aims of RDCRC Administrative Core.

Research Strategy: The purpose of a RDCRC is to expedite development and application of new knowledge in clinical research of specific importance to rare diseases. The RDCRC Administrative Core is responsible for the overall administration of the RDCRC (including policy, procedure, and fund allocation). Describe in detail, and by diagram if appropriate, the chain of responsibility for decision-making and administration. Include to whom the RDCRC Director (PD/PI) reports and the administrative structure as it relates to the investigators responsible for the clinical research projects. If advisory groups will be used, indicate their specific functions, composition and to whom they report. Describe a sound plan for communication (meetings, conference calls etc.) and participation of all personnel within the consortium. The description of the administrative unit of an RDCRC should detail how the activities and contribution of the collaborating investigators and institutions will be coordinated.

Describe the biostatistical support for the RDCRC in this section. The biostatistician from RDCRC will provide statistical support for protocol development and assist in study design and statistical data analysis. The biostatistician in collaboration with DMCC will also assist in the collection of epidemiologic information and quality assurance for database of pooled data for the RDCRC. The DMCC will work with NIH program staff to register RDCRN studies in dbGaP and will upload data on a regular basis according to the data sharing plan established by the Steering Committee.

Describe and justify any major changes proposed for structure of the RDCRC Administrative Core, as compared to the last grant period. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

Omit the Sharing Plans here as they were provided in the Overall section.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report  (RDCRC Administrative Core)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (RDCRC Administrative Core)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

When preparing your application in ASSIST, use Component Type ‘Project.’

Applications must include at least two clinical research projects that can characterize and more completely define the disease and its course for the rare diseases that are encompassed in their consortia; one of the projects must be a longitudinal study. These, in general, will be observational (non-interventional) such as longitudinal or natural history studies of patients with the given disease. These can be clinical trial-readiness projects (e.g., development of biomarkers for clinical trials, clinical outcome measures, etc.) and/or clinical trials.  

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 Projects)

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 Projects)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Research Projects)

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 Projects)

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 Projects)

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 Projects)

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 Projects)

Introduction to Application: For Resubmission applications, an Introduction to Application is required for the Clinical Research Projects.  

Specific Aims: Describe specific aims of the project.

Research Strategy: Describe the research strategy in enough detail so the scientific merit can be judged on the basis of the written application. Begin each project with a short section that clearly states how that project contributes to the objectives of the RDCRC as a whole.

Describe the rationale for the planned clinical studies and longitudinal assessment of subjects. Strategies for recruitment, retention, assessment, and analysis must be included. Data supporting the recruitment numbers are recommended. The study design and objectives should take into consideration what information regarding the rare disease population would be needed in order to pursue clinical trials in that rare disease. The applicants should approach the longitudinal study with the question: what knowledge/tools are needed regarding the rare disease in order to design efficient efficacy trials for this rare disease? Even if there are no treatments currently proposed for the rare diseases under study, the longitudinal study should be designed with the consideration that if a treatment were suddenly available for this rare disease, what knowledge (outcome measures, features of disease course, markers of disease or subpopulations of the rare disease that may alter disease course, etc.) about the rare disease over time would be important to have in order to design an appropriate treatment (efficacy) trial.

Depending on the state of knowledge of the particular diseases, the projects could include strategies for assessing current clinical interventions or future clinical trials. Both NINDS and NCI will support Phase I or Phase II, but not phase III clinical trials under this FOA. Although clinical trials can be supported through RDCRC, clinical trials are NOT a required component of an RDCRC. Each application must include a description and rationale of the study and the strategies for recruitment, retention, assessment, and analysis.

Data supporting recruitment numbers is recommended. Evidence of the ability to conduct clinical studies as well as demonstration of successfully recruiting and retaining study participants should be provided. Proposed longitudinal studies should be hypothesis-driven with defined quantifiable scientific objectives. Strategies for biomarker discovery studies utilizing specimens from the proposed studies are encouraged. Developing a patient registry is not considered a longitudinal study for this program. 

Incorporating the patients’ voice into clinical research studies as outcome measures is widely recognized as essential to fully capture both benefit and harm to the patients, as well as assess their health-related quality of life (HRQoL).  This is especially true for patients with rare diseases.   Applicants are encouraged to explore options for including and initially validating not only existing, but also emerging, patient-reported outcomes (PROs) such as the NIH-funded PROMIS® (www.nihpromis.org) and NeuroQoL (www.neuroqol.org).  Owing to their unique reliance on item-response theory (IRT) and a focus on domains rather than diseases, these new tools may facilitate assessment of symptoms and HRQoL in many, if not most, rare diseases.

A plan for a clinical research project must include provisions for rigorous data management, quality assurance, and safety monitoring. These monitoring activities are distinct from the requirement for study review and approval by an Institutional Review Board (IRB).

For clinical research projects (studies) completed in the last grant period, applicants should outline the scientific accomplishments and discuss the potential impact on the rare disease.   Applicants should also describe how they have partnered with the relevant patient advocacy groups and the roles these groups have played in the studies undertaken and engagement with patients.  Any difficulties in achieving the previously proposed specific aims should be addressed.  For the clinical research studies that were conducted during the prior funding period, a table should be provided listing the following information for each study: protocol number, protocol title, date study opened, date study closed and total number of accrual.  With the exception of the publication list, this information should be incorporated into the Preliminary Studies/Progress Report of each clinical research project. Proposed work can be a combination of: 1) the continuation of ongoing projects, 2) follow-on studies of current projects (e.g., a Phase II clinical trial based on a results from a Phase I trial), and/or 3) new projects.

Progress Report Publication List:  List and/or describe collaborative publications (or submitted manuscripts) by the investigative team including only those publications that are directly stemming from RDCRC activities from the prior funding period.

Human Subjects Protections: Describe plans for data and safety monitoring. This description should explain the plans for detecting, monitoring, and reporting any adverse event during a clinical study.  A specific data and safety monitoring (DSM) plan should be included in the Human Subjects section if the study is anticipated to begin within the first year of an award. A data and safety monitoring plan is required for all clinical studies. Depending upon the risk of the study, appropriate monitoring could include, for example, the PD/PI and IRB, a study monitoring committee, or an independent data and safety monitoring board (DSMB). NIH policy requires establishment of a DSMB for multi-site clinical trials involving interventions that entail potential risk to the participants. See https://grants.nih.gov/grants/policy/hs/data_safety.htm.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Omit the Sharing Plans here as they were provided in the Overall section.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide with the following additions:

Please provide a copy of a draft or IRB-approved clinical research protocol (Observational/Longitudinal Studies and clinical trials), along with informed consent forms.  

Planned Enrollment Report  (Clinical Research Projects)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Clinical Research Projects)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Pilot/Demonstration Project Clinical Research Program)

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 (Pilot/Demonstration Project Clinical Research Program)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot/Demonstration Project Clinical Research Program)

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) (Pilot/Demonstration Project Clinical Research Program)

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 (Pilot/Demonstration Project Clinical Research Program)

• 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 (Pilot/Demonstration Project Clinical Research Program )

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 (Pilot/Demonstration Project Clinical Research Program )

Introduction to Application: For Resubmission applications, an Introduction to Application is required for the Pilot/Demonstration Project Clinical Research Program.

Specific Aims: Describe specific aims of Pilot/Demonstration Project Clinical Research Program.  

Research Strategy:  The Pilot/Demonstration Clinical Research Program should propose a plan to support a spectrum of pilot/demonstration projects (at least one is required) that take maximum advantage of novel ideas or new clinical research opportunities in rare diseases research. Pilot projects are typically intended to generate feasibility data for novel ideas having the most promising clinical research potential.  Such projects may be collaborative among scientists within one or more RDCRC, or with scientists outside the RDCRC environment. The plan should address how candidate pilot projects will be continuously evaluated and prioritized for support by the RDCRC over the project period. Applicants should provide examples of eligible pilot projects, and the rationale for the proposed pilot projects. Examples of pilot/demonstration studies include development of novel laboratory assays and clinical instruments, development of tools for drug discovery (e.g., development of bioassays for screening compounds), analysis of extracellular RNAs as biomarkers of disease and/or response to therapeutics, retrospective chart review from different study sites. Depending on the state of knowledge of the particular diseases, the pilot studies could include strategies for assessing current therapeutic interventions, or phase I, I/II, or phase II clinical trials. Each pilot project should be proposed for a period of no more than two years.

Pilot Projects are a required component of RDCRC, and must be maintained throughout the entire term of the award. The NIH will monitor the activities of RDCRC sponsored pilot/demonstration to assure that there is adherence to the clinical research intention of the RDCRC program during the term of the award.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Omit the Sharing Plans here as they were provided in the Overall section.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report (Pilot/Demonstration Project Clinical Research Projects Program)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Pilot/Demonstration Project Clinical Research Program)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type ‘Project.’

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

SF424 (R&R) Cover (Career Development and Advancement Project)

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 (Career Development and Advancement Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Career Development and Advancement Project)

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) (Career Development and Advancement Project)

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 (Career Development and Advancement Project)

• 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 (Career Development and Advancement Project)

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

A minimum of $50,000 direct costs per year from the RDCRC budget must be dedicated to this program and be utilized to support the salary and research costs of candidates with outstanding potential. At least two trainees over 5 years must be supported and trained. The RDCRC should spend $250,000 over 5 years for career development. Institutional and outside support for this program is encouraged. Each junior level candidate (senior post-doctoral fellows, clinical fellows, and assistant professors/junior faculty) should have a mentor(s) and devote at least 3 calendar months of his/her effort to clinical research.

Funds from the Career Development and Advancement Project should be utilized to support clinical research activities, including partial salary support for the candidate, research personnel, supplies, travel, and/or other expenses. Career development funds should not be used for the purchase of any large equipment.

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 (Career Development and Advancement Project)

Introduction to Application: For Resubmission applications, an Introduction to Application is required for the Career Development and Advancement Project.

Specific Aims: Describe specific aims of the career development and advancement project.

Research Strategy: Each application must include a plan for career development and advancement of new investigator(s) for clinical research in rare diseases within their RDCRC.  Each RDCRC should provide a unique environment for clinical research in rare diseases that can be used to prepare new investigators for careers in this field and provide the opportunity for established scientists to re-orient their research careers toward rare diseases research through relevant courses, mentorship, and participation in clinical research.

The RDCRC must demonstrate a consistent and significant commitment to a career development and advancement program in clinical research. This program may be used to support advanced post-doctoral or clinical fellows, junior faculty (e.g. assistant professor rank, research faculty, instructors), or established investigators who wish to develop or refocus their careers on clinical research in rare diseases. RDCRC Career Development Programs are not intended for predoctoral candidates or junior level post-doctoral fellows (i.e., fewer than 2 years postdoctoral experience).

The description of this program should include the policies, criteria, and processes for selecting candidates, including special efforts to recruit individuals from groups underrepresented in the biomedical sciences. The plan should include the number and types of positions (e.g., advanced post-doctoral fellows, junior faculty, and established investigators) that will be made available, the criteria for eligibility and selection of candidates, and a description of the selection process. All applicants should provide a short description of types and qualifications of potential candidates, as well as the qualifications and research activities of mentors.

The Career Development and Advancement Project, as a required component of a RDCRC, must be maintained throughout the entire term of the award.

List individuals supported during the last award period, their scientific accomplishments while supported by the RDCRC, and how RDCRC support has advanced their clinical research careers in rare diseases. Provide the number of individuals from groups underrepresented in the biomedical sciences trained and the number of calendar months devoted to clinical research.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modification:

• Omit the Sharing Plans here as they were provided in the Overall section.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.   

Planned Enrollment Report  (Career Development and Advancement Project)

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

PHS 398 Cumulative Inclusion Enrollment Report (Career Development and Advancement Project)

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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.

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

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

This initiative is not subject to intergovernmental review.

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

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

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

For information on how your application will be automatically assembled for review and funding consideration after submission go to: https://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 Applying Electronically.

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 Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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 RDCRC 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 RDCRC 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 RDCRC that by its nature is not innovative may be essential to advance a field.

Significance

Does the RDCRC address an important problem or a critical barrier to progress in the field? If the aims of the RDCRC are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? 

Investigator(s)

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

Leadership:

Are the scientific qualifications and involvement of the PD/PI (RDCRC Director) and Administrative Director as well as scientific and administrative leadership capabilities and indicated time commitment sufficient for the requirements of the proposed RDCRC? 

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the RDCRC? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the RDCRC involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Additionally, for this FOA:

Rare Diseases Patient Population:

Is access to the proposed rare diseases patient population(s) adequate to achieve the goals of the program?

Is the study appropriately powered to achieve the stated aims?

Are adequate strategies for recruitment, retention, assessment, and analysis of subjects included, and is it feasible to achieve the target sample size?

Are appropriate measures to protect subject safety planned?

Multidisciplinary Team Involving Patient Advocacy Groups Collaborations:

Is there a plan to fully incorporate the relevant Patient Advocacy Groups within RDCRC structure and interactions?

Is Patient Advocacy Group participation described across the planned objectives (e.g., in addressing recruitment, retention, subject burden, and education)?

Are proposed activities appropriate for the Patient Advocacy Groups?

Research Team Interactions and Collaborations:

Will the proposed interactions likely contribute to the overall success of the RDCRC?

Is evidence provided that the RDCRC investigators will share requested information, participate in working groups or committees, and collaborate on activities of mutual interest both with the other participating RDCRC and with the NIH?

Is there evidence of effective and productive interactions/collaborations during the prior funding period?

Do applicants provide evidence of significantly contributing to RDCRN meetings, workshops or other related events during the previous funding period?

Environment

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

Institutional Commitment:

Is there an appropriate description of the existing or planned web site for education and research in rare diseases?

Are there features in the institutional environment that will facilitate the effective implementation of the proposed program? 

Is there institutional commitment to establishing the RDCRC as an integral part of its overall clinical research environment?

Will the institution align or adjust incentives and rewards to promote the academic mission of collaborative rare diseases research?

Is there commitment from the institutional leadership to protect the time of the investigators to pursue clinical research and mitigate the demands of providing patient care?

Is there commitment from the institutional leadership to support the career development of clinical researchers/trainees?  

Is the institutional leadership committed to this program and its goals in terms of providing assets specifically for the program, such as faculty support, specific equipment, dedicated space, or financial support?

Do the plans for integrating the activities of RDCRC clinical research projects with existing institutional resources (e.g., infrastructure to ensure subject safety and protections, biostatistical support, etc.), give confidence and sufficient evidence that such efforts are likely to be effective?

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

Are the plan(s) for the clinical research projects within the RDCRC of importance in this rare disease research area?

Investigator(s)

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

Are the investigators appropriately trained or experienced for conducting clinical research?

Innovation

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

Do the clinical approaches include innovative recruitment, assessment, or clinical trials methodology strategies?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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

Will the results of the proposed clinical research studies provide valuable resources and/or data to advance the field?

Is the study design optimal for achieving the stated goals?

Is the study appropriately powered to achieve the stated aims? Are the biostatistical approaches appropriate for the study?

Were recruitment goals met during the prior funding period?

Were subject recruitment and retention efforts effective?

Are the proposed recruitment goals realistic given subject availability as well as past performance?

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

Will the pilot projects proposed address an important problem in the field or overcome barriers in the rare disease(s) being studied in the RDCRC?

Does the plan attract and capture a spectrum of important new ideas and pilot studies in the field of rare diseases research?

Investigator(s)

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

Are the investigators leading the pilot projects proposed appropriate for this role in terms of expertise?

Innovation

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

Does the proposed plan address attracting new ideas and pilot studies within RDCRC institutions?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

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

Are the proposed pilot projects well-defined and do they address issues crucial to the overall theme of the RDCRC?  Is there a sufficient rationale for the proposed studies?

Is a plan for selection of future pilot studies well-defined and reasonable?

Is the proposed plan likely to lead to creation of a spectrum of pilot projects that have the potential to advance clinical research in rare diseases?

Will the proposed plan support pilot projects that leverage emergent clinical opportunities in rare diseases?

Environment

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

Is the environment appropriate to the proposed pilot projects?

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

Will the career development project have an effect in the targeted rare disease research field?

Does the career development project  present an opportunity for developing experts in a field where there may not otherwise be existing training programs?

Is expertise needed in the areas proposed for career development?

Investigator(s)

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

Is the plan for selecting candidates appropriate to the expected expertise?

Are the mentors and advisors appropriate for advancing the careers of trainees?

Innovation

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

Are any innovative approaches to identifying, mentoring or advancing the careers of individuals proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

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

Is the career development and mentoring plan adequate?

Is the process for selecting candidates likely to identify individuals who will benefit from the career development and advancement program and successfully transition to careers involving clinical research in rare diseases?

Does the proposed plan for identifying candidates address the recruitment and inclusion of individuals from groups underrepresented in the biomedical sciences?

Have the current status and clinical research activities of individuals who received training supported by the RDCRC during the prior funding period been provided, including any continuing RDCRC activities and were these activities adequate?

Environment

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

Is the environment appropriate for developing the careers of new investigators?

Reviewers should consider the review criteria below in determining the scientific merit of each RDCRC. Each assigned reviewer will provide one score for the Administrative Unit. The scientific merit of the Administrative Unit should be considered by reviewers in determining the Overall Impact score for the RDCRC.

Significance

Are the plan(s) for the overall administration of the RDCRC, coordination of clinical research, and the plan for communication and participation of personnel within the consortium well described?

Investigator(s)

Is the indicated time commitment of the Project Lead(s), collaborators, and other researchers sufficient for the leadership requirements of the proposed RDCRC?

Approach

Does the RDCRC provide appropriate biostatistical support?

Does the Administrative Unit provide a plan for coordination with Patient Advocacy Groups?

Are the leadership approach, governance and organizational structure outlined, and are they appropriate for the project?

Is there a clearly delineated plan to appropriately engage the relevant Patient Advocacy Groups (PAGs) within the RDCRC activities?

Is PAG participation and their role in the RDCRC described (for example, in recruitment, education, or other activities)?

Environment

Are there features in the institutional environment that are relevant to the effective implementation of the proposed program?

Is there institutional commitment to establishing the RDCRC as an integral part of its overall clinical research environment?

Will the institution align or adjust incentives and rewards to promote the academic mission of collaborative rare diseases research?

Is the institutional leadership committed to this program and its goals in terms of providing assets specifically for the program, such as faculty support, specific equipment, dedicated space, or financial support as a few examples?

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

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Children 

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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Since eligible applicants have at least a five-year history of funding under the RDCRN program, the committee will consider the progress made in the last funding period. In particular:

Are the progress and achievements described in the application directly attributable to RDCRC activities and relevant to the proposed clinical research?

Have prior specific aims been completed? If not, is rationale provided and are any difficulties in achieving the previously proposed specific aims addressed?  

Did the accomplishments in the prior funding period advance the field?

Are the justifications for adding new projects or discontinuing previous components appropriate and acceptable? Do the new research goals constitute logical extensions of the prior clinical research projects? Is there clear evidence that the continuation of any planned clinical research projects will lead to new findings that will advance the field?

For clinical research projects that will not be continuing in the renewal: was the project completed, or are the reasons why the project was discontinued made clear in the application?

Has the investigative team published or submitted collaborative manuscripts describing the projects completed during the prior funding period? Are publications listed in the application directly relevant to RDCRC activities?

Revisions

Not Applicable

As applicable for the RCDRC 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.

Plan for Streamlining the Protocol Approval Process

Are the plans to streamline the protocol approval process (e.g., IRB Share or a central IRB) included in the application and feasible for the clinical research proposed?

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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

Resource Sharing Plans

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

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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the NINDS for NINDS application(s) or NCI for NCI application(s) 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 will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. 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.  

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 

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

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.

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

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

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

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

The Principal Investigator of the RDCRC will have the primary responsibility for defining the details of the project within the guidelines of the FOA and for performing the scientific activity, and agrees to accept close coordination, cooperation, and participation of the NIH staff in those aspects of the scientific and technical management of the project described below. Specifically, awardees have primary responsibility as described below.

Awardees will retain custody of and have 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.

RDCRC Director and the DMCC Director

The Rare Diseases Clinical Research Consortium Directors (RDCRC Directors) with the assistance of the Data Management and Coordinating Center Director (DMCC Director) are responsible for the overall management of their RDCRC (Consortium) and coordination with the other Consortia. The relationship between the Consortia and the Data Management and Coordinating Center (DMCC) should be one of equal partners in the Rare Disease Clinical Research Network (Network).

Collaboration and Coordination

The collaboration of investigators between Consortia is highly encouraged based on shared interests and complementary talents. The planned collaborating sites within the Consortium must be ongoing and active. Plans for evaluating and removing or replacing non-productive sites of a Consortium must be in place for each Consortium.

Data Coordination and Management and Sharing

The awardees will have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS and NIH policies. The DMCC will develop a data management system with the input of the Steering Committee (See below: Areas of Joint Responsibilities). All Consortia will place their data at the DMCC. For complete roles and responsibilities of DMCC see companion FOA. The intention of the NIH is that the data collected within this Network will become a resource for the Rare Disease Community and be made available to the scientific community through an ORDR-governed data repository. Criteria and mechanisms for data sharing among investigators within the Network and with the scientific community will be developed by the Steering Committee. The DMCC will also coordinate with NIH program staff including registration with and data uploading of appropriate RDCRN studies to ORDR-governed data repository (through dbGaP, a database for genotypes and phenotypes, National Library of Medicine). Data transfer to dbGaP is expected to occur on regular basis according to the data sharing policy for RDCRN established by the Steering Committee and as approved by NIH staff.

Publication and Presentation of Study Findings

Timely publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgment of the Rare Disease Clinical Research Network, ORDR, NCATS, and NIH ICs support. The Steering Committee (See below: Areas of Joint Responsibilities) will establish unifying procedures and criteria for presentation and publication of data developed within the Rare Disease Clinical Research Network so that these procedures and criteria are consistent across the Network.

Federally Mandated Regulatory Requirements

Each institution participating in the Rare Diseases Clinical Research Network is required to meet DHHS regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include:

• methods for assuring that each institution at which Rare Diseases Clinical Research Network investigators are conducting clinical studies has registered with the Office of Human Research Protections (OHRP; http://www.hhs.gov/ohrp/) and has a Federal wide Assurance; that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to patient entry; that active protocols are reviewed at least annually by the IRB, and that amendments are approved by the IRB.

• methods for assuring or documenting that each patient, or patient's parent/legal guardian, gives fully informed consent to participation in a research protocol prior to the initiation of the clinical study.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

An NIH Project Scientist from each participating IC will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards. For IC specific roles and responsibilities of Project Scientists contact the appropriate NIH IC Program Official listed in Section VII. Agency Contact.

One representative from ORDR, NCATS will be designated to serve as the Program Coordinator for this cooperative agreement program (RDCRN). The ORDR, NCATS Program Coordinator for RDCRN and one Project Scientist from each participating IC will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond normal program stewardship for awards.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Monitoring Performance

The ORDR, NCATS Program Coordinator and IC Project Scientists will assist the Steering Committee (See below: Areas of Joint Responsibilities) in the development of procedures for monitoring the performance of the clinical studies. This may include participation in periodic on-site monitoring with respect to compliance with protocol specifications, quality control and accuracy of data recording, and accrual.

Publication and Presentation of Clinical Studies Findings

The NIH staff may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the clinical studies to the investigator community and other interested scientific and lay organizations. Co-authorship by the NIH staff will be subject to approval in accordance with the NIH policies regarding staff authorship of publications resulting from extramural awards.

The Government, via the ORDR, NCATS Program Coordinator, IC Project Scientists and Program Officials, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. Information obtained from the data may be used by NIH staff for the preparation of internal reports on the activities of the clinical studies. However, awardees will retain custody of and have primary rights to all data developed under these awards.

Program Stewardship

The assigned Program Official from participating NIH ICs will be responsible for normal programmatic stewardship and monitoring of this award and approval of new pilot studies. The Program Official will not serve as the substantively involved IC Project Scientist. They may receive input and recommendations from other NIH staff in monitoring the awards.

Areas of Joint Responsibilities include:

All investigators within each Consortium and the DMCC must be willing to work cooperatively and collaboratively both within their Consortium and with other Consortia. Each Consortium is expected to send two Consortium participants to biannual meetings in the Washington, D.C. or Bethesda MD area.

Network Steering Committee Membership and Meeting Attendance

A Steering Committee will be established to serve as the main governing body of the cooperative network. At a minimum, the Steering Committee will be composed of one representative from each of the Consortium, one representative from the DMCC, the chairperson of Coalition of Patient Advocacy Group (CPAG), the NIH Program Coordinator from ORDR, NCATS, and other participating IC Project Scientists. All members are expected to actively participate in all Steering Committee activities. The combined vote of NIH membership may never exceed 33 percent.

Each Consortium Principal Investigator will be designated the Consortium Director. Each Consortium Director will be a voting member of the Network Steering Committee and participate in all Committee activities and decisions including, but not limited to, conference calls and special subcommittees as may be necessary.

The NIH Program Coordinator from ORDR, NCATS and the Project Scientists from the participating ICs will serve on the Steering Committee and will participate in all Committee activities, including, but not limited to, meetings, conference calls, subcommittees, and special committees. They will assist in development of operating policies, quality control procedures, and policies that require cooperative action.

The Chairperson of the Steering Committee will be selected by the Steering Committee from among the non-Federal members during one of the early meetings of the Committee to be convened by the NIH Program Coordinator from ORDR, NCATS. All major decisions will be made by the Steering Committee. The Committee will meet at least three times during the first 12 months of the program and at least semi-annually thereafter. As needed, the Steering Committee may establish subcommittees for special purposes. It is expected that most of the work of the Steering Committee will be performed in these subcommittees. All Consortia and DMCC must abide by decisions of the Steering Committee.

The Steering Committee will have responsibility of facilitating the conduct of the clinical studies, promoting trans-Consortium collaboration, establishing and updating the content of the web resource site, and establishing procedures for reporting results of Consortium studies. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. An Arbitration Panel composed of three members will be convened. It will have three members: a designee of the Network 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 awardee. This special dispute resolution procedure does not alter awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

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Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Laura A. Mamounas, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: mamounal@ninds.nih.gov

Katrina A. Gwinn, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5745
Email: gwinnk@ninds.nih.gov

Beth-Anne Sieber, Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-5680
Email: sieberb@ninds.nih.gov

Rashmi Gopal-Srivastava, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-402–4336
Email: gopalr@mail.nih.gov

William D. Merritt, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-276-6137
Email: merrittw@mail.nih.gov

Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9223
Email: nindsreview.nih.gov@mail.nih.gov

Tijuanna Decoster Ph.D.
National Institute of Neurological Disorders and Stroke (NINDS)
Telephone: 301-496-9231
Email: decostert@mail.nih.gov

Ruthann Rand
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-451-4238
Email: randrudy@mail.nih.gov

Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-676-6303
Email:  woodwars@mail.nih.gov

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), under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92, and under the Rare Diseases Act of 2002, Public Law 107-280-Nov. 6, 2002.